Old mice recover the ability to produce IgG and high-avidity antibody following irradiation with partial bone marrow shielding

Abstract

The splenic plaque-forming-cell (PFC) response to trinitrophenylated bovine gamma globulin of 18- to 20-month-old mice is markedly depressed, with a preferential loss of indirect (IgG) PFC and high-avidity-antibody-secreting cells compared to 6- to 8-week-old animals. The anti-trinitrophenyl response of old mice, whose peripheral lymphoid system has been reconstituted from their own bone marrow after irradiation while their bone marrow was partially shielded, includes high-avidity and IgG PFCs relatively comparable to those of normal young mice. If young mice are irradiated while their bone marrow is partially shielded and given purified splenic T cells from either old or young donors during recovery from irradiation, then the avidity distribution and the ratio of IgG/IgM PFCs they produce in response to trinitrophenylated bovine gamma globulin reflects the characteristic immune response of the T-cell donor. These results are consistent with the hypothesis that the bone marrows of old and young mice are similar with regard to the spectrum of B-cell clones that they can generate and that it is peripheral regulatory effectors that are responsible for much of the age-related change in the immune response. In addition, if one calculates the PFC avidity distribution taking into account those cells whose secretion of antibody was inhibited by anti-idiotype autoantibodies, then it is clear that there are more high-avidity B cells present in old mice than are detected by the conventional plaque-inhibition assay. Thus, the reduced avidity of the PFC response of old mice appears to be, at least in part, due to down regulation by anti-idiotype autoantibodies.